POS0948 SIX YEARS TREATMENT WITH TNF-α INHIBITORS DOES NOT LEAD TO LONG-TERM CONTINUOUS HYPERMINERALIZATION IN PATIENTS WITH ANKYLOSING SPONDYLITIS
Authors: M. Siderius, A. Spoorenberg, E. Van der Veer, F. G. M. Kroese, S. Arends
Journal: Annals of the Rheumatic Diseases (2022)

Background In a previous study, we showed that the bone turnover balance favored bone formation, especially mineralization, during the first years of treatment with TNF-α inhibitors (TNFi) 1 in patients with ankylosing spondylitis (AS). Objectives To explore if this effect continues during more long-term TNFi treatment. Therefore our goal was to investigate the prolonged course of serum levels of bone turnover markers (BTM) during 6 years of TNFi treatment in patients with AS. Methods Included were consecutive AS outpatients from the UMCG GLAS cohort who were treated with TNFi for at least 6 years. Patients were excluded when they used bisphosphonates. Data for a specific visit was coded as missing when patients either had experienced a fracture or received systemic corticosteroids within 1 year from that particular visit regarding the possible effect on BTM. Standardized follow-up visits were performed at baseline (before start of TNFi), 3 and 6 months, 1, 2, 4 and 6 years. Serum markers of collagen resorption sCTX, bone regulation OC, collagen formation PINP, and bone mineralization BALP were measured. Z-scores were calculated to correct for the normal influence of age and gender using a healthy reference population. Generalized estimating equations were performed to analyze BTM Z-scores over time within patients. Results 53 AS patients were eligible for analyses: 66% were male, mean (SD) age was 38.5 ± 11.3 years, median (IQR) symptom duration was 16 (9-25) years, 87% were HLA-B27+, mean ASDAS was 3.8 ± 1.0, and median CRP 14 (7-27) mg/L. Etanercept, infliximab or adalimumab was prescribed as first TNFi in 60%, 2% and 38% of patients, respectively. 26% (n=14) of patients switched to a second TNF-α inhibitor during follow-up. Disease activity showed rapid and sustained improvement after start of TNFi (Figure 1). At group level, collagen resorption marker sCTX Z-score did not significantly change during treatment. Bone regulation marker OC Z-score was only significantly increased at 3 months compared to baseline. Collagen formation marker PINP Z-score showed significantly increased levels at 3 and 6 months and 2 years. Bone mineralization marker BALP Z-score was significantly increased at all time points up to and including 2 years and decreased thereafter. Only a few patients still had higher BTM values above the normal range (+2 SD) (Figure 2). The net effect of collagen metabolism corrected for the normal influence of age and gender (PINP Z-score – sCTX Z-score) confirmed that the initial balance was in favor of collagen formation; this increase was only significant at 6 months compared to baseline. Conclusion In AS patients receiving long-term TNFi, the bone turnover balance favored bone formation during the first 2 years of treatment. Thereafter, at group level, serum levels of BTM returned to levels not significantly different from baseline. Therefore, 6 years of treatment with TNF-α inhibitors did not seem to lead to long-term continuous hypermineralization in patients with AS. References [1]Arends et al. Arthritis Res Ther. 2012;14(2):R98 Disclosure of Interests Mark Siderius: None declared, Anneke Spoorenberg Consultant of: AbbVie, Novartis Pharma, Pfizer, UCB Pharma, Lilly, Grant/research support from: Novartis Pharma, Pfizer, Eveline Van der Veer: None declared, Frans G.M. Kroese: None declared, Suzanne Arends: None declared